Urinary tract infections (UTIs) are among the most common infections affecting humans, and can be particularly problematic for females, who are prone to recurrent episodes of UTIs. Anti-adhesive therapy represents a novel therapeutic approach to the prevention of bacterial infections, since adhesion to host tissue is the necessary first step in the development of numerous infections. In addition, antibiotic-resistant bacteria can still be susceptible to anti-adhesive therapies, which is an advantage since these infections can be very difficult to treat with current antibiotics. The goal of this research is to determine the molecular mechanisms by which cranberry metabolites can prevent the adhesion of E. coli to urinary epithelial cells. While some clinical studies have shown that cranberry juice consumption can prevent UTIs in women experiencing recurrent infections, information is needed on the mechanism of this action so that cranberry therapy can become integrated into established medical practices. In particular, we are focusing on P-fimbriated E. coli, which cause the most serious type of UTI, acute pyelonephritis (kidney infection). These infections often develop when P-fimbriated E. coli ascend from the bladder. Therefore, our experimental model focuses on quantifying how cranberry can impair the adhesion of E. coli to bladder uroepithelial cells. Atomic force microscopy (AFM) is a molecular tool that we use to directly measure adhesion forces between uropathogenic bacteria and bladder epithelial cells. In Aim 1, adhesive force measurements are made in the presence of urine from volunteers that have consumed cranberry juice components, to establish the dose and time of exposure needed to induce an anti-adhesive response. In Aim 2, we will characterize the differences in response to cranberry treatment using urinary epithelial cells of women with recurrent UTIs, compared to epithelial cells from healthy women. This work can lead to the rationale design of clinical studies that will allow for more widespread application of cranberry therapy to prevent UTIs. PUBLIC HEALTH RELEVANCE: Urinary tract infections (UTIs) are among the most common infectious diseases, particularly affecting females. This work seeks to further the understanding of the mechanisms by which consumption of cranberry juice can be used as a preventive therapy for UTIs.